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Query: UNIPROT:P41181 (collecting duct)
 5,183 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Water homeostasis is regulated in large part by the proper operation of the urinary concentrating mechanism. In the renal inner medulla, urea recycling from the inner medullary collecting duct to the inner medullary interstitium is thought to be essential for the production of a concentrated urine; however, it has not been possible to test this hypothesis in humans. Recently, a unique combination of genetic abnormalities has been described: absence of Kidd blood group antigens and absence of carrier-mediated urea transport in erythrocytes. Because animal studies indicate a similarity between urea transport in red blood cells and the nephron, it was postulated that patients without the Kidd antigen might lack facilitated urea transport in their kidneys. Hence, their ability to concentrate urine maximally was measured. Current models of nephron function would predict that in the complete absence of urea transport, the maximal concentrating ability would be around 800 to 900 mosM/kg H2O. Two homozygous patients had a moderate decrease in maximal concentrating ability (UosM,max = 819 mosM/kg H2O); a heterozygote also had some limitation. These studies raise the possibility that the erythrocyte urea transporter and the kidney urea transporter are encoded by a single gene (detected by the mutational loss of the Kidd antigen) and that a lack of facilitated urea transport impairs urea recycling in the kidney and, hence, maximal urinary concentrating ability.
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PMID:Urinary concentrating ability in patients with Jk(a-b-) blood type who lack carrier-mediated urea transport. 149 76

Urea transport across the terminal inner medullary collecting duct (IMCD) is mediated by a urea transporter that is stimulated by vasopressin (AVP) or hyperosmolarity. To determine whether hyperosmolarity stimulates urea transport by an adenylyl cyclase-dependent or -independent mechanism, terminal IMCDs were perfused with 10 microM forskolin followed by an increase in osmolality or with increasing osmolality followed by 10 nM AVP. In both protocols, stimulating adenylyl cyclase caused an additive increase in urea permeability (Purea) to that stimulated by hyperosmolarity. Next, we investigated whether hyperosmolarity stimulates the same urea transporter as AVP by studying the inhibitor profile and IMCD subsegment response of hyperosmolarity-stimulated urea transport and comparing it to properties already demonstrated for AVP-stimulated urea transport. In terminal IMCDs, luminal phloretin (250 microM) reversibly inhibited Purea by 63%. Thiourea (100 mM) inhibited Purea by 73% at two different levels of osmolality, 690 and 290 mosmol/kgH2O. The half-maximal inhibitory concentration (K1/2) for thiourea at 690 mosmol/kgH2O was not significantly different from the K1/2 value at 290 mosmol/kgH2O, suggesting that stimulation by hyperosmolarity is related to an increase in the Vmax for the urea transporter. Finally, we found that hyperosmolarity did not stimulate Purea in the initial IMCD. In summary, the data suggests that hyperosmolarity stimulates urea transport by an adenylyl cyclase-independent mechanism. However, the inhibitor profile and the IMCD subsegment response for hyperosmolarity-stimulated and AVP-stimulated Purea are similar, suggesting that both hyperosmolarity and AVP stimulate the same urea transporter.
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PMID:Characteristics of osmolarity-stimulated urea transport in rat IMCD. 162 10

We have used the isolated perfused tubule technique, measurements of adenosine 3',5'-cyclic monophosphate (cAMP) content in single tubules, and freeze-fracture electron microscopy to study the basis of high vasopressin-independent (basal) osmotic water permeability (Pf) in the terminal inner medullary collecting duct (IMCD) of the rat. The results confirmed the observation that the basal Pf of the terminal IMCD is considerably higher than that of the initial IMCD. They also showed that the basal Pf of the terminal IMCD is regulated by in vivo factors related to water intake, such that a very high vasopressin-independent Pf can be induced in isolated tubules by prior in vivo thirsting. Tubules from thirsted rats did not display elevated urea permeabilities, nor did they exhibit measurable cAMP levels in the absence of exogenous vasopressin, indicating that the high basal Pf was not due to residual binding of vasopressin to its receptors. Freeze-fracture studies in thirsted rats demonstrated the presence of intramembrane particle (IMP) clusters in both initial and terminal IMCD, with more in the latter. Water loading of the rats suppressed the incidence of clusters almost entirely but did not fully suppress the basal Pf in the terminal IMCD, raising the possibility that a component of transepithelial water transport may occur independently of the vasopressin-regulated IMP clusters. On the basis of these results, we conclude that the vasopressin-independent Pf in the terminal IMCD can be stably elevated to very high levels in response to in vivo thirsting. This elevation appears to be due to a chronic conditioning effect mediated by unknown in vivo factors and is not due to the short-term cAMP-mediated regulatory effect of vasopressin.
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PMID:Regulation of collecting duct water permeability independent of cAMP-mediated AVP response. 165 34

The stimulation of alpha-1 adrenergic receptors in the mammalian nephron increases sodium reabsorption. In this study, alpha-1 adrenergic receptors in the inner medullary collecting duct (IMCD) cells were examined by radioligand binding technique. The IMCD cells were prepared from the rabbit kidney by incubating the inner medullary slices with collagenase and treating the isolated cells with hypotonic solution to lyse cells other than IMCD cells. The equilibrium binding of [3H]prazosin to IMCD cell homogenate was measured after incubation for 30 min at 25 degrees C in the absence (total binding) and the presence (nonspecific binding) of 100 microM phentolamine. The specific binding (the difference between total and nonspecific binding) of [3H]prazosin was saturable with a Bmax of 30 fmol/mg of protein and Kd of 0.9 nM. The displacement of [3H]prazosin binding to IMCD cells by adrenergic antagonists and agonists displayed the order of potency: beta-4-hydroxyphenyl-ethyl-amino-tetralone greater than phentolamine greater than naphazoline greater than epinephrine greater than yohimbine greater than norepinephrine greater than phenylephrine greater than propranolol. Because IMCD cells in the kidney have a hypertonic environment, the specific binding of [3H] prazosin to IMCD cells was also measured in a buffer that was made hypertonic (1200 mOsmol/kg of water) with NaCl and urea, the major solutes of the renal medulla. The hyperosmolality increased the Kd of [3H]prazosin to 5.2 mM without a change in its Bmax.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Alpha-1 adrenergic receptors in renal medullary collecting duct cells. 168 13

Sharks, skates, and rays (Elasmobranchii) have evolved unique osmoregulatory strategies to survive in marine habitats. These adaptations include a complex renal countercurrent system for urea retention. The fine structure of the complete renal tubular epithelium has yet to be elucidated in any species of cartilagenous fish. The present study, which is a companion to our recent paper describing the ultrastructure of the neck and proximal segments of the elasmobranch nephron, uses thin sections and freeze-fracture replicas to elucidate the fine structural organization of the intermediate, distal, and collecting duct segments of the little skate, Raja erinacea, renal tubule. The epithelium of the intermediate, distal, and collecting duct segments consists of two major cell types: nonflagellar cells, the major epithelial cell type; and flagellar cells, described elsewhere. The intermediate segment consists of six subdivisions lined by cuboidal-columnar cells with variously elaborated microvilli and interdigitations of lateral and basal cell plasma membranes, as well as some subdivisions with distinctive vesicles and granules. The distal segment consists of two subdivisions, both of which are lined by a simple epithelium, and are distinguished from each other by their distinctive contents; dense bodies and granules. The collecting duct segment also has two subdividions, the first lined by a simple columnar epithelium and the second by a stratified columnar epithelium. Both subdivisions have apical secretory granules. The present findings show a more highly specialized and diverse epithelium lining the renal tubule of these cartilagenous fish than is found in either of the "adjacent" phylogenetic taxa, Agnatha or Ostheichthyes, suggesting significant differences among these groups in transepithelial transport mechanisms and renal function.
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PMID:The fine structure of the elasmobranch renal tubule: intermediate, distal, and collecting duct segments of the little skate. 178 55

We have shown that urea transport across the terminal inner medullary collecting duct (terminal IMCD) is mediated by a vasopressin-stimulated, facilitated diffusion process exhibiting properties consistent with a transporter. To investigate whether hypertonic NaCl, as exists in vivo in the inner medulla, affects urea permeability, we studied isolated perfused rat terminal IMCD segments. Perfusate and bath osmolality were varied symmetrically by adding or removing NaCl or mannitol. Urea permeability rose progressively when osmolality was increased with NaCl or mannitol from 290 to 690 mOsm/kg H2O in the absence of vasopressin; there was no further increase at 890 mOsm/kg H2O. In the presence of 10(-8) M arginine vasopressin, urea permeability increased when NaCl was added to raise osmolality from 290 to 490 mOsm/kg H2O but there was no further increase at 690 mOsm/kg H2O. When 1 mM 8-bromo cyclic AMP was added to the bath, raising NaCl still increased urea permeability. These results suggest that urea transport across the rat terminal IMCD is regulated both by vasopressin and by osmolality at values present in the renal inner medulla. Osmolality seems to activate urea transport across the rat terminal IMCD by mechanisms distinct from those of vasopressin or cyclic AMP.
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PMID:An independent effect of osmolality on urea transport in rat terminal inner medullary collecting ducts. 190 26

We examined the action of high (2 x 10(-8)M) and low (6 x 10(-9)M) concentrations of atrial natriuretic factor (ANF) on water and urea transport in the rat inner medullary collecting duct (IMCD) using the in vitro microperfusion technique. We measured the hydraulic conductivity (Lp x 10(-6) cm/atm per second) and both lumen-to-bath (Pu(lb] and bath-to-lumen (Pu(bl)) 14C-urea permeabilities (Pu x 10(-5) cm/s) in the absence and in the presence of vasopressin (VP). High concentrations of ANF were able to inhibit the maximum activity of (50 microU/ml) VP-stimulated Lp but physiological concentration of ANF inhibit only submaximum activity (10 microU/ml) of VP-stimulated Lp. The hydrosomotic effect of dibutyryl-cyclic 3.5 adenosine monophosphate (cAMP) (10(-4)M) was unchanged by high concentrations of ANF (2 x 10(-8)M). Also we found that high (10(-4)M) and low (10(-6)M) concentrations of exogenous cyclic 3,5-guanosine monophosphate (GMP) while unable to change the Lp in the absence of VP, decreased the maximum activity of VP-stimulated Lp significantly. We also found that ANF inhibits partially and in a reversible manner the VP-stimulated Pu(lg) but not the VP-stimulated Pu(bl). These results demonstrated that plasma concentrations of ANF observed during volume expansion (10(-10)M) are able to inhibit submaximum activity of VP-stimulated (10 microU/ml) Lp in the rat IMCD, this effect seems to occur before cAMP formation and it appears to be mediated by cGMP. ANF (6 x 10(-9)M) also reduced the VP-stimulated urea outflux.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effect of atrial natriuretic factor and cyclic guanosine monophosphate on water and urea transport in the inner medullary collecting duct. 196 94

A mathematical model has been developed to simulate hypertonic urine formation in the renal medulla. The model uses published values of membrane transport parameters, as have other models, but is unique in its representation of the three-dimensional anatomy of the medulla. The model successfully predicts measured fluid flows, osmolarities, and NaCl and urea concentrations. The model results are presented in the companion to this paper [A. S. Wexler, R. E. Kalaba, D. J. Marsh. Am. J. Physiol. 260 (Renal Fluid Electrolyte Physiol. 29): F368-F383, 1991.]. In this paper we provide tests of the sensitivity of model performance to variations in the description of the anatomy and in membrane transport parameters. From these studies we conclude that 1) strict counterflow arrangements are required in the outer stripe to prevent loss of NaCl to the systemic circulation, 2) the radial organization in the inner stripe materially improves performance of the inner medulla, 3) radial organization of the inner medulla is essential to hypertonic urine formation there, 4) the model is most sensitive to variation in collecting duct parameters, and 5) reabsorption of urea in the distal tubule improves system performance. The results support the claim that the three-dimensional structure, as captured in the model, provides a crucial framework for the production of hypertonic urine.
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PMID:Three-dimensional anatomy and renal concentrating mechanism. II. Sensitivity results. 200 Sep 55

The present in vitro microperfusion study examined whether chlorpropamide (CPM) has a direct effect on hydraulic conductivity (Lp x 10(-6) cm/atm.sec) and 14C-urea permeability (Pu x 10(-5) cm/sec) in the middle and distal inner medullary collecting duct (IMCD) obtained from acutely water-loaded Wistar rats and rats homozygous for diabetes insipidus (DI). CPM (10(-4) M) added to the bath fluid increased the Lp in the water-loaded Wistar rats from -0.05 +/- 0.13 to 6.25 +/- 0.74 (p less than 0.01) and in the DI rats from 0.05 +/- 0.01 to 5.95 +/- 0.84 (p less than 0.01), but had no effect when it was added to the perfusate. CPM stimulated Lp in a dose-dependent manner with the threshold effect at 10(-6) M. However, the addition of CPM (10(-4) M) to submaximal concentration of VP in the bath fluid did not increase the Lp. Furthermore, CPM was unable to block the inhibitory action of PGE2 on the vasopressin (VP)-stimulated Lp. On the contrary, PGE2 blocked the CPM-stimulated Lp. CPM (10(-4) M) in the peritubular fluid was able to cause a significant rise of the Pu from 13.5 +/- 0.8 to 17.3 +/- 1.0 reversibly, which represented 16% of maximum stimulated effect produced by 50 microU/ml of VP. Thus, pharmacological doses of CPM added to the peritubular side have a direct effect on terminal IMCD increasing water and urea permeability in the absence of VP, but this drug does not potentiate the VP-stimulated water transport in the IMCD. Our results were unable to confirm the hypothesis that CPM potentiates the VP-antidiuresis by the inhibition of PGE2 action in the rat IMCD.
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PMID:Effect of chlorpropamide on water and urea transport in the inner medullary collecting duct. 200 36

Myo-inositol (MI) is involved in the adaptation to hyperosmolality. Its uptake by rat inner medullary collecting duct (RIMCD) cells has not been studied. Compared with cells grown in isotonic media, those grown in hyperosmolality display marked enhancement in [3H]MI uptake [counts/min (cpm).microgram protein-1.2 h-1] from 217 +/- 23 to 718 +/- 64, P less than 0.001. This is mimicked by the supplementation with 300 mM mannitol (638 +/- 59, P less than 0.001) but not by 300 mM urea. The increment in [3H]MI is observed at 37 degrees C but not at 4 degrees C. MI uptake is Na+ dependent in cells grown both in hyperosmolal or isotonic media. At least 12 h of hyperosmolality are needed to enhance MI uptake, and reexposure to isotonic media for at least 24 h is required for the enhancement to reverse. The effects of the microtubular inhibitor, nocodazole (10 micrograms/ml), and the protein synthesis inhibitor, cycloheximide (30 micrograms/ml), were studied. Cells grown with nocodazole show unimpaired enhancement of MI uptake. Cycloheximide exposure (16 h) does not affect MI uptake in isotonic media (182 +/- 23 vs. 191 +/- 15), but inhibited enhanced MI uptake in hyperosmolality (822 +/- 53 in the absence vs. 331 +/- 24 in the presence of cycloheximide, P less than 0.001). We conclude that hyperosmolality stimulates the synthesis of a protein, most likely an Na-MI cotransporter, that markedly enhances MI uptake. This process may be critical to the osmoregulation of RIMCD cells.
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PMID:Myo-inositol uptake by rat cultured inner medullary collecting tubule cells: effect of osmolality. 203 49


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